E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
short bowel syndrome and intestinal failure |
síndrome de intestino corto y fallo intestinal |
|
E.1.1.1 | Medical condition in easily understood language |
short gut |
intestino corto |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10049416 |
E.1.2 | Term | Short-bowel syndrome |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of weekly SC apraglutide in reducing parenteral support dependency |
Evaluar la eficacia de la administración semanal de apraglutida por vía s.c. desde el punto de vista de la reducción de la dependencia de NP |
|
E.2.2 | Secondary objectives of the trial |
To evaluate selected parameters indicative of clinical efficacy • To evaluate the safety and tolerability of apraglutide compared with placebo • To assess the PK of apraglutide |
Evaluar determinados parámetros indicativos de la eficacia clínica • Evaluar la seguridad y la tolerabilidad de apraglutida en comparación con el placebo • Evaluar la farmacocinética (FC) de apraglutida |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed informed consent for this trial prior to any trial specific assessment. 2. Male and female subjects with SBS-IF, receiving parenteral support (PS), secondary to surgical resection of the small intestine with either stoma or colon-in-continuity (CIC). 3. Subject must require PS at least 3 days per week and be considered stable. 4. No restorative surgery intended to change PS requirements in the trial period. 5. Age ≥18 years at screening. |
1. Haber firmado el consentimiento informado para este estudio antes de realizar ninguna de las evaluaciones específicas del estudio. 2. Pacientes de ambos sexos con SIC-FI, que reciban nutrición parenteral (NP), derivado de la resección quirúrgica del intestino delgado que presenten estoma o colon en continuidad (CEC). 3. Que el paciente precise NP al menos 3 días a la semana y se considere que es estable. 4. No tener previsto someterse a una intervención de cirugía restauradora para modificar la demanda de NP durante el período del estudio. 5. Edad ≥ 18 años en el momento de la selección. |
|
E.4 | Principal exclusion criteria |
1.Pregnancy or lactation. 2.Major abdominal surgery in the last 6 months prior to screening. 3.History of cancer (including colon carcinoma) or clinically significant lymphoproliferative disease within ≤5 years, except for adequately treated basal cell skin cancer. 4.Evidence of active inflammatory GI conditions in the previous 6 months. 5.Evidence of decompensated heart failure. 6.Evidence of severe renal or hepatic impairment. 7.Any previous use of growth factors such as growth hormone (GH), native GLP-2, GLP-1, or GLP-2 or GLP-1 analogues should be discussed with the Investigator. |
1. Mujeres embarazadas o en período de lactancia. 2. Haberse sometido a una intervención de cirugía mayor abdominal en los 6 meses anteriores a la selección. 3. Antecedentes de cáncer (incluido el carcinoma de colon) o de enfermedad linfoproliferativa clínicamente importante en el transcurso de ≤5 años, salvo los casos de cáncer cutáneo de células basales tratado adecuadamente. 4. Evidencia de enfermedad inflamatoria intestinal activa en los 6 meses anteriores. 5. Evidencia de insuficiencia cardíaca descompensada. 6. Evidencia de función renal o hepática insuficiente. 7. El uso anteriormente de factores de crecimiento (como la hormona del crecimiento [HC], GLP-2 o GLP-1 endógenos o análogos del GLP-2 o del GLP-1) deberá ser hablado con el investigador. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Relative change from baseline in actual weekly PS volume at Week 24. |
Variación relativa en la semana 24 respecto al período inicial en el volumen semanal real de NP. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
•Subjects who achieve a reduction of at least 1 day per week of PS from baseline at Weeks 24 / 48. •Relative change from baseline in actual weekly PS volume at Weeks 12 / 24 / 48. •SBS-IF patients reaching enteral autonomy at Weeks 24 / 48. •At least 20% reduction of PS volume from baseline at Weeks 20 / 24. •Calorie reduction in the PN at Weeks 24. •Change from baseline on QoL measures at Weeks 24 / 48. •Apraglutide PK parameters (baseline through Week 48). |
• Pacientes que en la semana 24 / 48 alcancen una reducción de al menos 1 día a la semana en la NP respecto al período inicial. • Variación relativa en la semana 12 / 24 / 48 respecto al período inicial en el volumen semanal real de NP. • Pacientes SIC-FI que en la semana 24 / 48 alcancen la autonomía enteral. • Pacientes que presenten al menos un 20 % de reducción en el volumen de NP en las semanas 20 / 24 respecto al período inicial. • Reducción calórica en la NP en la semana 24 • Variación entre el período inicial y la semana 24 / 48 en los resultados de los cuestionarios de calidad de vida. • Parámetros farmacocinéticos de apraglutida desde el período inicial hasta la semana 48. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
specified at point E.5.2 |
especificado en el apartado E.5.2 |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 43 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
China |
Israel |
Japan |
Korea, Republic of |
Taiwan |
United States |
Belgium |
Denmark |
France |
Germany |
Italy |
Norway |
Poland |
Spain |
Sweden |
United Kingdom |
Czechia |
Argentina |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 16 |